Biomechanics of human fetal hearts with critical aortic stenosis

Critical aortic stenosis (AS) of the fetal heart causes a drastic change in the cardiac biomechanical environment. Consequently, a substantial proportion of such cases will lead to a single-ventricular birth outcome. However, the biomechanics of the disease is not well understood. To address this, we performed Finite Element (FE) modelling of the healthy fetal left ventricle (LV) based on patient-specific 4D ultrasound imaging, and simulated various disease features observed in clinical fetal AS to understand their biomechanical impact. These features included aortic stenosis, mitral regurgitation (MR) and LV hypertrophy, reduced contractility, and increased myocardial stiffness. AS was found to elevate LV pressures and myocardial stresses, and depending on severity, can drastically decrease stroke volume and myocardial strains. These effects are moderated by MR. AS alone did not lead to MR velocities above 3 m/s unless LV hypertrophy was included, suggesting that hypertrophy may be involved in clinical cases with high MR velocities. LV hypertrophy substantially elevated LV pressure, valve flow velocities and stroke volume, while reducing LV contractility resulted in diminished LV pressure, stroke volume and wall strains. Typical extent of hypertrophy during fetal AS in the clinic, however, led to excessive LV pressure and valve velocity in the FE model, suggesting that reduced contractility is typically associated with hypertrophy. Increased LV passive stiffness, which might represent fibroelastosis, was found to have minimal impact on LV pressures, stroke volume, and wall strain. This suggested that fibroelastosis could be a by-product of the disease progression and does not significantly impede cardiac function. Our study demonstrates that FE modelling is a valuable tool for elucidating the biomechanics of congenital heart disease and can calculate parameters which are difficult to measure, such as intraventricular pressure and myocardial stresses

European Study on Maternal and Fetal Management of Fetal Supraventricular Tachyarrhythmia:Proposed Protocol for an International Project

> Objectives: This European protocol is designed to estimate the efficacy of transplacental digoxin administered intravenously to the mother in sustained fetal supraventricular tachyarrhythmias (FSVT) with or without cardiac failure and in intermittent runs of FSVT with cardiac failure. The natural history of FSVT is evaluated in self-limited runs of FSVT without cardiac failure. Study structure: The fetal criteria for inclusion in the study are: gestational age 200 beats/min. The maternal criteria include no prior treatment with digoxin or drugs effecting fetal heart rate and hemodynamics, and no contraindication to digoxin. Doppler fetal echocardiography is utilized for the diagnosis of the type of FSVT, sequential evaluation, and assessment of fetal hemodynamics. Fetuses are assigned two groups: Group I includes all fetuses with sustained FSVT and those with intermittent runs and cardiac failure; Group II comprises fetuses with intermittent runs and no cardiac failure. Fetuses in Group I will be treated. Group II will receive no treatment initially and will be observed. Treatment is based on a acute loading phase with digoxin administered intravenously to the mother for a period of 7 days. Doses are adjusted to through levels of maternal digoxin, maternal clinical condition, and electrocardiogram. If sinus rhythm is obtained, a maintenance phase follows with oral digoxin. Another drug, according to local experience and preference, is added to oral digoxin if digoxin intravenously fails to restore sinus rhythm and gestational age is <36 weeks. Post natal outcome will be followed by sequential clinical and Holter examinations. The data collected will be reviewed in a blinded fashion. The collection of the data for the protocol requires extensive information on the maternal, fetal, and long-term follow-up studies. They are detailed in the Appendix section. Expected results: We propose to obstetricians and pediatric cardiologists involved in fetal cardiology a rationale for the management and treatment of FSVT. Our expectation is to obtain a controlled study on a large number of cases at an international scale and thus provide a homogeneous maternal and fetal therapeutic strategy for FSVT